반응 #635921

반응 방정식

Cesium carbonate

3-hydroxy-N-(5-methylpyrazin-2-yl)-5-[(3S)-tetrahydrofuran-3-yloxy]benzamide

6-bromo-3,4-dihydro-2H-isoquinolin-1-one

2,2,6,6 tetramethyl-3,5-heptanedione

→

desired compound

N-(5-Methylpyrazin-2-yl)-3-[(1-oxo-1,2,3,4-tetrahydroisoquinolin-6-yl)oxy]-5-[(3S)-tetrahydrofuran-3-yloxy]benzamide

용매

NMP

반응 조건

후처리

1. 1
   여과The reaction mixture was filtered through diatomaceous earth
2. 2
   세척the filter pad washed thoroughly with DCM and methanol
3. 3
   농축The filtrate was concentrated in vacuo, water (20 mL)
4. 4
   workup.ADDITIONwas added to the residue
5. 5
   추출the mixture extracted with ethyl acetate (3×50 mL)
6. 6
   세척The combined organic phases were washed with water (2×10 mL), brine (20 mL)
7. 7
   건조dried (MgSO4)
8. 8
   기타evaporated in vacuo
9. 9
   기타The crude product was chromatographed on silica
10. 10
    세척eluting with a gradient of 0-5% methanol in DCM

실험 절차

Cesium carbonate (812 mg, 2.50 mmol) was added to a solution of 3-hydroxy-N-(5-methylpyrazin-2-yl)-5-[(3S)-tetrahydrofuran-3-yloxy]benzamide (262 mg, 0.83 mmol), 6-bromo-3,4-dihydro-2H-isoquinolin-1-one (226 mg, 1.0 mmol), copper (I) iodide (158 mg, 0.83 mmol) and 2,2,6,6 tetramethyl-3,5-heptanedione (0.7 mL, 3.3 mmol) in NMP (9 mL) and the stirred mixture heated at 160° C. in a microwave reactor for 8 hours. The reaction mixture was filtered through diatomaceous earth and the filter pad washed thoroughly with DCM and methanol. The filtrate was concentrated in vacuo, water (20 mL) was added to the residue and the mixture extracted with ethyl acetate (3×50 mL). The combined organic phases were washed with water (2×10 mL), brine (20 mL), dried (MgSO4) and evaporated in vacuo. The crude product was chromatographed on silica, eluting with a gradient of 0-5% methanol in DCM, to give the desired compound a white solid (190 mg). 1H NMR δ (CDCl3): 2.17 (1H, m), 2.22-2.29 (1H, m), 2.56 (3H, s), 2.94-3.02 (2H, m), 3.49-3.59 (2H, m), 3.90-4.01 (4H, m), 5.00 (1H, s), 6.01 (1H, s), 6.77-6.80 (1H, m), 6.83 (1H, s), 6.96 (1H, d), 7.16 (1H, s), 7.26 (1H, d), 8.06 (1H, d), 8.15 (1H, s), 8.49 (1H, s), 9.54 (1H, s); m/z 461 (M+H)+, 459 (M−H)−

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